Peeters T L, Depoortere I, Macielag M J, Dharanipragada R, Marvin M S, Florance J R, Galdes A
Department of Medical Research, Katholieke Universiteit te Leuven, Belgium.
Biochem Biophys Res Commun. 1994 Jan 28;198(2):411-6. doi: 10.1006/bbrc.1994.1060.
Studies on the physiological role of motilin, and more recently, on the relationship between motilin and erythromycin A, have been hampered by the lack of antagonists. We now have discovered such a compound. ANQ-11125 displaces motilin bound to an homogenate of rabbit antral smooth muscle tissue. The dissociation constant (pKd) was 8.16 +/- 0.10. However, ANQ-11125 did not induce contractions of segments of rabbit duodenum, except at high concentrations. In the presence of 1 microM ANQ-11125 the dose response curves of erythromycin-A, De(N-methyl)-N-ethyl-8,9 anhydroerythromycin A 6,9-hemiacetal and motilin were shifted about one log unit to the right, but the responses to ACh and Substance P were unaffected. Schild-analysis showed the competitive nature of the interaction and allowed the calculation of the pA2: 7.03 +/- 0.05 (motilin curves) and 7.55 +/- 0.06 (EM-523 curves). This is the first report of a motilin antagonist. Its properties definitively prove that motilides are motilin agonists.
由于缺乏拮抗剂，对胃动素生理作用的研究，以及最近对胃动素与红霉素A之间关系的研究受到了阻碍。我们现在发现了这样一种化合物。ANQ - 11125能置换与兔胃窦平滑肌组织匀浆结合的胃动素。解离常数（pKd）为8.16±0.10。然而，ANQ - 11125除了在高浓度时，不会引起兔十二指肠节段的收缩。在存在1μM ANQ - 11125的情况下，红霉素A、去（N - 甲基）- N - 乙基 - 8,9 - 脱水红霉素A 6,9 - 半缩醛和胃动素的剂量反应曲线向右移动了约一个对数单位，但对乙酰胆碱和P物质的反应未受影响。Schild分析显示了这种相互作用的竞争性，并允许计算pA2：7.03±0.05（胃动素曲线）和7.55±0.06（EM - 523曲线）。这是关于胃动素拮抗剂的首次报道。其特性明确证明胃动素类药物是胃动素激动剂。
